A Crossover Study to Assess the Effects of Vorinostat (MK0683, SAHA) in Patients With Advanced Cancer - Full Text View

Sponsor:	Merck
Information provided by:	Merck
ClinicalTrials.gov Identifier:	NCT00632931

Purpose

A 2-period, crossover study to assess the effects of MK0683 (vorinostat) on the QTc interval in patients with relapsed or refractory advanced cancer.

Condition	Intervention	Phase
Advanced Cancer Relapsed Advanced Cancer Refractory	Drug: vorinostat Drug: Comparator: placebo (unspecified)	Phase I

Study Type:	Interventional
Study Design:	Allocation: Randomized Control: Placebo Control Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Single Blind (Subject) Primary Purpose: Treatment
Official Title:	A Randomized, Partially-Blind, Placebo-Controlled, 2-Period Crossover Study to Assess the Effects of a Single Dose of Vorinostat on the QTc Interval in Patients With Advanced Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Suberoylanilide hydroxamic acid

U.S. FDA Resources

Further study details as provided by Merck:

Primary Outcome Measures:

Change From Baseline in QTcF at 0.5 Hours [ Time Frame: Baseline and 0.5 hours ] [ Designated as safety issue: Yes ]
The Fridericia correction of the QT interval (QTcF) was determined at each time point from five replicate measurements. The change from baseline in QTcF was calculated by subtracting the QTcF value at each timepoint from the QTcF baseline (predose) value.
Change From Baseline in QTcF at 1 Hour [ Time Frame: Baseline and 1 hour ] [ Designated as safety issue: Yes ]
Fridericia correction of the QT interval (QTcF) was determined at each time point from five replicate measurements. The change from baseline in QTcF was calculated by subtracting the QTcF value at each timepoint from the QTcF baseline (predose) value.
Change From Baseline in QTcF at 2 Hours [ Time Frame: Baseline and 2 hours ] [ Designated as safety issue: Yes ]
The Fridericia correction of the QT interval (QTcF) was determined at each time point from five replicate measurements. The change from baseline in QTcF was calculated by subtracting the QTcF value at each timepoint from the QTcF baseline (predose) value.
Change From Baseline in QTcF at 3 Hours [ Time Frame: Baseline and 3 hours ] [ Designated as safety issue: Yes ]
The Fridericia correction of the QT interval (QTcF) was determined at each time point from five replicate measurements. The change from baseline in QTcF was calculated by subtracting the QTcF value at each timepoint from the QTcF baseline (predose) value.
Change From Baseline in QTcF at 4 Hours [ Time Frame: Baseline and 4 hours ] [ Designated as safety issue: Yes ]
The Fridericia correction of the QT interval (QTcF) was determined at each time point from five replicate measurements. The placebo-corrected change from baseline in QTcF was calculated by subtracting the QTcF change from baseline for placebo at each timepoint from the QTcF change from baseline for vorinostat at each timepoint.
Change From Baseline in QTcF at 8 Hours [ Time Frame: Baseline and 8 hours ] [ Designated as safety issue: Yes ]
The Fridericia correction of the QT interval (QTcF) was determined at each time point from five replicate measurements. The change from baseline in QTcF was calculated by subtracting the QTcF value at each timepoint from the QTcF baseline (predose) value.
Change From Baseline in QTcF at 12 Hours [ Time Frame: Baseline and 12 hours ] [ Designated as safety issue: Yes ]
The Fridericia correction of the QT interval (QTcF) was determined at each time point from five replicate measurements. The change from baseline in QTcF was calculated by subtracting the QTcF value at each timepoint from the QTcF baseline (predose) value.
Change From Baseline in QTcF at 24 Hours [ Time Frame: Baseline and 24 hours ] [ Designated as safety issue: Yes ]
The Fridericia correction of the QT interval (QTcF) was determined at each time point from five replicate measurements. The change from baseline in QTcF was calculated by subtracting the QTcF value at each timepoint from the QTcF baseline (predose) value.

Enrollment:	25
Study Start Date:	June 2007
Study Completion Date:	July 2008
Primary Completion Date:	May 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental Arm A: Drug/Placebo	Drug: vorinostat A 2-part, crossover study. Part 1: Arm A: Single dose of vorinostat 800 mg capsules (Period 1) crossing over to Single dose of vorinostat Placebo capsules (Period 2) Arm B: Single dose of vorinostat Placebo capsules (Period 1) crossing over to Single dose of vorinostat 800 mg capsules (Period 2). Part 2: All patients will receive 400 mg vorinostat capsules once daily. Treatment will continue until disease progression or intolerable toxicity. Drug: Comparator: placebo (unspecified) A 2-part, crossover study. Part 1: Arm A: Single dose of vorinostat Placebo capsules (Period 2) Arm B: Single dose of vorinostat Placebo capsules (Period 1).
B: Experimental Arm B: Placebo/Drug	Drug: vorinostat A 2-part, crossover study. Part 1: Arm A: Single dose of vorinostat 800 mg capsules (Period 1) crossing over to Single dose of vorinostat Placebo capsules (Period 2) Arm B: Single dose of vorinostat Placebo capsules (Period 1) crossing over to Single dose of vorinostat 800 mg capsules (Period 2). Part 2: All patients will receive 400 mg vorinostat capsules once daily. Treatment will continue until disease progression or intolerable toxicity. Drug: Comparator: placebo (unspecified) A 2-part, crossover study. Part 1: Arm A: Single dose of vorinostat Placebo capsules (Period 2) Arm B: Single dose of vorinostat Placebo capsules (Period 1).

Arms

Assigned Interventions

A: Experimental

Arm A: Drug/Placebo

Drug: vorinostat

A 2-part, crossover study. Part 1: Arm A: Single dose of vorinostat 800 mg capsules (Period 1) crossing over to Single dose of vorinostat Placebo capsules (Period 2) Arm B: Single dose of vorinostat Placebo capsules (Period 1) crossing over to Single dose of vorinostat 800 mg capsules (Period 2). Part 2: All patients will receive 400 mg vorinostat capsules once daily. Treatment will continue until disease progression or intolerable toxicity.

Drug: Comparator: placebo (unspecified)

A 2-part, crossover study. Part 1: Arm A: Single dose of vorinostat Placebo capsules (Period 2) Arm B: Single dose of vorinostat Placebo capsules (Period 1).

B: Experimental

Arm B: Placebo/Drug

Drug: vorinostat

A 2-part, crossover study. Part 1: Arm A: Single dose of vorinostat 800 mg capsules (Period 1) crossing over to Single dose of vorinostat Placebo capsules (Period 2) Arm B: Single dose of vorinostat Placebo capsules (Period 1) crossing over to Single dose of vorinostat 800 mg capsules (Period 2). Part 2: All patients will receive 400 mg vorinostat capsules once daily. Treatment will continue until disease progression or intolerable toxicity.

Drug: Comparator: placebo (unspecified)

A 2-part, crossover study. Part 1: Arm A: Single dose of vorinostat Placebo capsules (Period 2) Arm B: Single dose of vorinostat Placebo capsules (Period 1).

Detailed Description:

Merck Duration of Treatment : vorinostat; treatment will continue until disease progression or intolerable toxicity is reached

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patient has a histologically-confirmed metastatic or locally advanced solid tumor that has failed to respond to standard therapy, progressed despite standard therapy or for which standard therapy does not exist
Patient has life expectancy of greater than 3 months
Patient is able to swallow capsules

Exclusion Criteria:

Patient has had chemotherapy, radiotherapy or biological therapy 2 weeks prior to taking study drug
Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of signing informed consent
Patient has active CNS metastases and/or carcinomatous meningitis
Patient has primary central nervous system tumor
Patient has a history of drug or alcohol abuse
Patient has Hepatitis B or C
Patient is HIV positive
Patient has active infection or has received intravenous antibiotics, antiviral or antifungal agents 2 weeks before taking study drug

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00632931

Sponsors and Collaborators

Merck

Investigators

Study Director:

Medical Monitor

Merck

More Information

Additional Information:

(MedWatch - FDA maintained medical product safety Information) This link exits the ClinicalTrials.gov site

(PhRMA Clinical Study Results Database - web-based repository for clinical study results) This link exits the ClinicalTrials.gov site

(Merck: Patient & Caregiver U.S. Product Web Site) This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Merck & Co., Inc. ( Executive Vice President, Clinical and Quantitative Sciences )
Study ID Numbers:	2008_515, MK0683-070
Study First Received:	February 29, 2008
Results First Received:	January 18, 2010
Last Updated:	February 22, 2010
ClinicalTrials.gov Identifier:	NCT00632931 History of Changes
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Anticarcinogenic Agents
Anti-Inflammatory Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Vorinostat
Physiological Effects of Drugs
Enzyme Inhibitors
Protective Agents
Pharmacologic Actions

Neoplasms
Analgesics, Non-Narcotic
Sensory System Agents
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Peripheral Nervous System Agents
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on March 18, 2010